GPR rules for specific fatty acid oxidation reactions MAR02121, MAR02122, MAR02123

[manas-kohli]

Hey, this is a bit of a question/suggestion but I was looking at GPR rules for these reactions (MAR02121, MAR02122, MAR02123) and the genes listed for these reactions are CPT2, CPT1B but these are mitochondrial and as far as the literature suggests, are not expressed in the peroxisome. Actually further to this, peroxisomes don't appear to import carnitine species but instead export fatty acid-carnitine species for further oxidation in the mitochondria. They import activated fatty acids, which appear to have relevant reactions in the peroxisome already in Human1. I think simply deleting these reactions are a bit problematic but I'd like to hear what the Human1 curators think about this and whether these reactions are supported in the literature.

[Devlin-Moyer]

Yea I have come across a lot of similar issues with fatty acid oxidation reactions (see most of the issues between #736 and #801), and while I think it would be good to systematically go through all of the peroxisomal fatty oxidation reactions to fix issues like this, most of the issues I've already opened about other issues with fatty acid oxidation reactions haven't been resolved yet (because nobody else has had time to double check that all of the fixes I propose are correct), so I've been hesitant to open any more issues about things like this

[Devlin-Moyer]

in the case of these specific reactions, I suspect that the appropriate fix would be similar to the changes made to MAR03481 and MAR06779 in #773

[Devlin-Moyer]

While it is true that MAR03011, MAR03013, and MAR03014 represent ATP-dependent import of palmitoyl-, linoleoyl-, and arachidonyl-CoA, respectively, MAR02122 and MAR02123 can only export linoleoyl- and arachidonyl- acyl chains from peroxisomes to the cytosol, so MAR03013 and MAR03014 don't really replace MAR02122 and MAR02123. MAR02121 is reversible, so half of it is more accurately represented by MAR03011, but running MAR02121 + MAR02788 in the other direction does seem to be the only pathway for exporting palmitoyl-CoA from peroxisomes in Human-GEM. Based on this paper, it's not clear to me if palmitoyl-, linoleoyl-, and arachidonyl-CoA should be able to leave peroxisomes without first being oxidized to shorter acyl-CoAs, but if they can be exported, it doesn't seem like carnitine should be involved, since the peroxisomal acylcarnitine transferases only seem to work with acyl-CoAs shorter than palmitoyl-, linoleoyl-, and arachidonyl-CoA.